Evaluation of C-Reactive Protein Prior to and On-Treatment as a Predictor of Benefit From Atorvastatin: Observations From the Anglo-Scandinavian Cardiac Outcomes Trial

Study Questions:

Among subjects enrolled in the ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial), was C-reactive protein (CRP) associated with increased risk of cardiovascular outcomes?

Methods:

ASCOT enrolled subjects with total cholesterol levels ≤250 mg/dl, who were then randomized to atorvastatin (10 mg/day) or placebo. All subjects had a diagnosis of hypertension and three or more additional cardiovascular disease (CVD) risk factors. At baseline, participants had no prior history of myocardial infarction or currently treated angina. This analysis was a case-controlled study of 485 CVD cases that were matched by age, sex, and study entry time, to 1,367 controls.

Results:

Over a median follow-up period of 5.5 years, a total of 1,852 subjects were eligible for inclusion in this current analysis. Of these subjects, 131 were excluded for missing values. The mean age of the study population was 64.7 years, and 84.7% were male. Baseline low-density lipoprotein (LDL) levels and log-transformed CRP were predictive of CVD events (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.10-1.56 for LDL and OR, 1.19; 95% CI, 1.05-1.34 for CRP). Inclusion of CRP into the Framingham risk model improved risk prediction modestly. There was no evidence of an interaction between LDL and CRP and treatment effect on CVD events. A 6-month on-treatment LDL among those randomized to atorvastatin was associated with a significant reduction in CVD events (OR, 0.41; 95% CI, 0.22-0.75). In contrast, CRP below the median (1.83 mg/L) compared with CRP above the median was not associated with a significant reduction in CVD events (OR, 0.86; 95% CI, 0.49-1.51).

Conclusions:

The investigators concluded that among hypertensive patients with additional CVD risk factors, CRP did not improve prediction of events in a clinically meaningful way. Reduction in CRP associated with statin therapy was not a predictor of CVD outcomes alone or in combination with LDL levels.

Perspective:

This is an interesting finding. Using data from ASCOT, these results support the continued use of traditional risk factors as a means of identifying patients at increased risk for CVD outcomes.

Clinical Topics: Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Statins, Hypertension

Keywords: Myocardial Infarction, Follow-Up Studies, Risk Factors, Heptanoic Acids, Pyrroles, Lipoproteins, LDL, Cholesterol, C-Reactive Protein, Case-Control Studies, Biological Markers, Cardiovascular Diseases, Hypertension


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